3-amino-1,2,4-triazole inhibits macrophage NO synthase.
Biochem Biophys Res Commun, 1992/2/28;183(1):150-5.
Buchmüller-Rouiller Y[1], Schneider P, Betz-Corradin S, Smith J, Mauël J
Affiliations
PMID: 1371917
Impact factor: 3.322
Abstract
Murine macrophages activated by interferon-gamma and lipopolysaccharide become leishmanicidal through a process involving L-arginine-derived nitrogen oxidation products. Both nitrite secretion and parasite killing by activated macrophages were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino-1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3-amino-1,2,4-triazole, was without effect. Our results suggest that besides its known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is an inhibitor of NO synthase. The resemblance between the tautomeric form of 3-amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate for NO synthase, might be responsible for the observed inhibition.
MeSH terms
Amino Acid Oxidoreductases; Amitrole; Animals; Cytosol; Dose-Response Relationship, Drug; Interferon-gamma; Leishmania; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Mice, Inbred CBA; Nitric Oxide; Nitric Oxide Synthase
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